**1. Introduction**

Type 2 diabetes mellitus (T2D) is a syndrome of disturbed metabolic pathways of sacharides (carbohydrates), proteins and fat due to various influence of eight pathophysiologic mechanisms described as ominous octet: disturbed dynamics of insulin secretion, reduced production of incretins in gut, hyperglucagonaemia, increased production of glucose from liver, disturbed endocrine function of adipose tissue, insulin resistance, increased activity of sodium glucose transporter 2 (SGLT2) resulting in increased reabsorption of glucose from renal tubules and malfunction of hypothalamic centers for satiety and hunger. [1] These mechanisms are induced by different genetic and environmental factors. [2, 3]

In previous centuries, clinical symptoms of T2D lead to therapeutic attempts based on lifestyle, diet and on oral antidiabetic drugs, mostly sulfonylureas.

The discovery of insulin by Paulesco in 1921 [4] and its final introduction to human medicine by Banting, Collip, Best and Macleod in 1922 [5] saved many lives of people with T1D. However, in T2D insulin was mostly used as an ultimate therapeutic alternative.

In 1957, the discovery of metformin resulted in reduction of hyperglycaemia without hypoglycaemias. In the course of several decades, metformin proved to be a relatively effective mean to reduce body mass and cardiovascular complications. In addition, in persons on metformin the frequency of neoplasms appears to be lower. Today, metformin undoubtedly remains the drug worthy of choice for the majority persons with T2D. [6]

At the end of the 20th century, a new concept of pathophysiologic approach to T2D was suggested by Bruns [7] under the descriptive term "complementary therapy", and, independently by Berger [8, 9] as "supplementary therapy".

Important role in the intensification of insulin regimens played insulin pens which were produced since the year 1983. [10] At the beginning of the 21st century, insulin pumps (first implemented by John Pickup in 1978 [11]) and intensive selfmonitoring were also applied in people with T2D. [12–14] Despite of pumps many persons with T2D were unable to reach the expected metabolic improvement until incretin receptor agonists and gliflozins have been made available. [15, 16]

In 1974, the first glucometer (Ames) was introduced into clinical practice, followed by tenths of other glucometers [17–19], Continuous Glucose Monitors (CGM) [20] and/or Flash Glucose Monitors (FGM) [21]. Today, these devices have become mandatory means (together with HbA1c analysers [22]) to assess the metabolic control. Scientific inventions from the last 100 years were applied in official statements and guidelines. [23–25]

This overview introduces promoting insights and better understanding of pathophysiologic approach to various treatments of T2D. Purpose of the presented case reports and single-centre "real world trials "is to motivate to education and to implementation of incretins and/or gliflozins and/or insulin analogs and/or insulin pumps in daily routine of diabetes care.

### **2. Prerequisites for a pathophysiologic approach to T2D management**

#### **2.1 Therapeutic education**

Lifestyle and education of people with chronic disorders have been recognised as an essential part of treatment. Many anonymous dedicated enthusiasts have created a solid platform for effective therapy. Some of them became famous educators, however, most of them remained unnoticed in everyday practice.

The Diabetes Education Study Group (DESG) of the European Association for the Study of Diabetes (EASD), was founded in 1977 [26] and the Therapeutic Patient Education (TPE) became a goal of many respected bodies in the world.

The DESG aimed to improve the quality of life through educational programmes designed to foster independence for the patient, to improve the quality of metabolic control, to emphasise the prevention and to encourage research. The DESG organised activities all over the Europe, published more than 30 Teaching letters and Series of the 5-min education basics. In eastern countries, the DESG workshops (Bucharest, 1982, Balatonfuered, 1985, Warsaw, 1987, Weimar, 1989, Olomouc, 1991) supported the cooperation between health care providers (physicians, teachers, psychologists, nurses, dietitians, social workers) and patients. (**Figure 1**) Therefore, the adopted 5- day scheduled teaching programs created by Assal, Berger and Jörgens in Genf and Düsseldorf [27] could be spread throughout Europe. Workshops at Grimentz,

**5**

*Pathophysiologic Approach to Type 2 Diabetes Management: One Centre Experience 1980–2020*

Capri, Celano, Assisi, Chillworth, Cambridge, Winchester, Windsor, Sesimbra, etc.,

Process of TPE consists of three parts: teaching knowledge, training skills and formating attitudes. These principles have also been considered in our pathophysi-

Insulin pens opened the door to comfortable insulin administration thereby making the intensive regimens acceptable at work, at school, at leisure, during

In 1983, the first models of a MAnual Device for Insulin (MADI) proved to be a useful aid to injection of U-40 insulin either as a needle pen or as a catheter pen. [10] Within a few years other injectors appeared. [30, 31] Six models of a new type of MADI for insulin U-40, U-80 and U-100 were developed. [32] (**Figure 2**) In the needle pen (**Figure 3**) a sliding cover prevents the contamination of the needle which remains invisible in the course of injection and might be reused without sterilization. [33] In the catheter pen (**Figure 4**) the catheter remained inserted in subcutaneous tissue for 3 days. A syringe-like interchangeable plastic reservoir (3 ml) was refilled from insulin vials with any kind of soluble insulin. Actual insulin administration occurred by twisting the cap after subcutaneous insertion

To date, about one hundred of various types of insulin or incretin needle-pens have been distributed all over the world. (**Figure 5**) Most of them are disposable

motivated to look at issues from various angels.

**2.2 Technical support**

of needle or catheter.

travels, etc.

**Figure 1.**

ologic approach to treatment of T2D in daily routine. [28, 29]

*Abstract Book from the last workshop of the Eastern DESG in Olomouc (1991).*

*2.2.1 Development and clinical implementation of insulin pens*

*DOI: http://dx.doi.org/10.5772/intechopen.96237*

*Pathophysiologic Approach to Type 2 Diabetes Management: One Centre Experience 1980–2020 DOI: http://dx.doi.org/10.5772/intechopen.96237*

**Figure 1.** *Abstract Book from the last workshop of the Eastern DESG in Olomouc (1991).*

Capri, Celano, Assisi, Chillworth, Cambridge, Winchester, Windsor, Sesimbra, etc., motivated to look at issues from various angels.

Process of TPE consists of three parts: teaching knowledge, training skills and formating attitudes. These principles have also been considered in our pathophysiologic approach to treatment of T2D in daily routine. [28, 29]
